Associations of antimicrobial use with antimicrobial susceptibility at the calf level in bacteria isolated from the respiratory and digestive tracts of veal calves before slaughter.

OBJECTIVES Antimicrobial drugs are frequently administered in veal calves, but investigations on associations with antimicrobial susceptibility of bacteria are scarce and convey partly contradictory findings. The aim of this study was to investigate associations of antimicrobial use (AMU) during the fattening period with antimicrobial susceptibility shortly before slaughter. METHODS Detailed treatment data of 1905 veal calves from 38 farms were collected prospectively during monthly farm visits for 1 year (n = 1864 treatments, n = 535 visits); 1582 Escherichia coli, 1059 Pasteurella multocida and 315 Mannheimia haemolytica were isolated from rectal and nasopharyngeal swabs collected before slaughter and subjected to antimicrobial susceptibility testing by microdilution. Associations of antimicrobial treatments with resistant isolates were investigated at the calf level. RESULTS Associations of AMU with antimicrobial resistance were observed using generalized linear models. For E. coli, the odds of being resistant were increased with increased AMU (OR 1.36 when number of treatments >1, P = 0.066). Use of tetracyclines was associated with resistance to tetracycline (OR 1.86, P < 0.001) and use of penicillins was associated with resistance to ampicillin (OR 1.66, P = 0.014). No significant associations were observed for P. multocida (use of aminoglycosides: OR 3.66 for resistance to spectinomycin, P = 0.074). For M. haemolytica, the odds of being resistant were increased with increased AMU (OR 4.63, P < 0.001), and use of tetracyclines was associated with resistance to tetracycline (OR 6.49, P < 0.001). CONCLUSIONS Occurrence of resistant bacteria shortly before slaughter was associated with AMU in veal calves. Prudent and appropriate use may contribute to limit the selection of resistant bacteria on veal farms

Farm-level risk factors for digital dermatitis in dairy cows in mountainous regions.

Reduction of risk factors for bovine digital dermatitis (BDD) is crucial in current disease control. However, risk factors that might arise especially in mountainous regions are unknown until now, and an adapted BDD control program is consequently missing. The objective of this observational case-control study was to identify farm-level risk factors for BDD in dairy herds in mountainous regions. To investigate predictors for the occurrence of BDD, 100 farms were visited and information about herd characteristics and management practices, potentially relevant explanatory variables for either introduction or establishment of BDD, were gathered by completing a questionnaire with the farmer or herd manager. Within-herd prevalences of BDD assessed during 3 routine claw trimmings with an interval of 6 mo before the survey were used to define cases (BDD within-herd prevalence of ≥26% during each claw trimming) and controls (no BDD cases in each of the 3 routine claw trimmings before the survey). Data were analyzed using 2 separate binomial generalized linear models according to either establishment or introduction of BDD. After prescreening, 15 of 23 explanatory variables were included in the final analysis, which showed 3 variables related to introduction and establishment, each being significantly associated with the occurrence of BDD within a farm. Results of model 1 (i.e., aspects related to BDD introduction) revealed that access to mountain pastures during the summer season (odds ratio, 95% confidence interval: 0.12, 0.04-0.35), participation in dairy shows (0.32, 0.11-0.94), and the number of new animals introduced into the farm during the last 2 yr (1.28, 1.12-1.52) were significantly associated with the occurrence of BDD. Model 2 (i.e., aspects related to BDD establishment) showed that cows kept in freestalls were at higher risk for BDD compared with those kept in tiestalls (20.65, 1.59-649.37). Furthermore, number of days between diagnosis and treatment of a BDD lesion (10.31, 3.55-81.21) and the amount of concentrate feeding (median 5 kg) per cow and day (7.72, 2.46-6.47) were positively associated with BDD occurrence. In conclusion, the findings of this study provide a set of risk factors that are associated with BDD status within herds in mountainous regions. These results may help in development of adapted control programs for BDD in dairy cows

Self-help for stress and burnout without therapist contact: An online randomised controlled trial

Interventions designed to reduce stress and burnout may be costly and access is limited. This study examined the effectiveness of a self-help book, using Acceptance and commitment therapy (ACT) to target stress and burnout in a randomised controlled online trial without any therapist contact. Participants were recruited through a newsletter of a health insurance company. Participants ( N = 119) who reported at least moderate levels of stress were randomly assigned to an immediate intervention ( n = 61) or a waitlist group ( n = 58). Measures before and after the intervention assessed stress, burnout (primary outcomes), depression, well-being, emotion regulation (secondary outcomes) and ACT-specific constructs. Compared to the waitlist group, participants in the immediate intervention group reported lower stress and burnout and higher psychological flexibility at post-assessment. Effects between groups were large for stress ( d = 0.9), moderate to large for burnout ( d = 0.5–0.8) and large for psychological flexibility ( d = 0.8). All primary and most secondary outcomes and ACT processes continued to improve in the 3-month-follow-up period. Results suggest that an ACT self-help book without any therapist contact is effective in reducing stress and burnout for various occupations. Thus, it may provide a cost-effective public health intervention for reducing stress and burnout

Two new cases of anti-Ca (anti-ARHGAP26/GRAF) autoantibody-associated cerebellar ataxia

Recently, we discovered a novel serum and cerebrospinal fluid (CSF) autoantibody (anti-Ca) to Purkinje cells in a patient with autoimmune cerebellar ataxia (ACA) and identified the RhoGTPase-activating protein 26 (ARHGAP26; alternative designations include GTPase regulator associated with focal adhesion kinase pp125, GRAF, and oligophrenin-1-like protein, OPHN1L) as the target antigen. Here, we report on two new cases of ARHGAP26 autoantibody-positive ACA that were first diagnosed after publication of the index case study. While the index patient developed ACA following an episode of respiratory infection with still no evidence for malignancy 52 months after onset, neurological symptoms heralded ovarian cancer in one of the patients described here. Our finding of anti-Ca/anti-ARHGAP26 antibodies in two additional patients supports a role of autoimmunity against ARHGAP26 in the pathogenesis of ACA. Moreover, the finding of ovarian cancer in one of our patients suggests that anti-Ca/anti-ARHGAP26-positive ACA might be of paraneoplastic aetiology in some cases. In conclusion, testing for anti-Ca/anti-ARHGAP26 should be included in the diagnostic work-up of patients with ACA, and an underlying tumour should be considered in patients presenting with anti-Ca/ARHGAP26 antibody-positive ACA

Identifizierung und Quantifizierung der Transforming Growth Factor beta Rezeptor-Isotypen 1 und 2 sowie von Betaglykan in humanen Knochenbiopsien und primären, humanen Knochenzellkulturen

$\bf Problem:$ Der Wuchsfaktor TGF beta ist für den Knochenstoffwechsel wichtig, er fördert Proliferation und Differenzierung der Knochenzellen. Die Signale werden über die TGF-$\beta$ I- und II- Rezeptoren weitergeleitet. Der TGF-$\beta$ III-Rezeptor (im Knochen Betaglykan) nimmt nicht direkt an der Signalübermittlung teil. $\bf Methode:$ Untersucht wird die T$\beta$R-I- bis -III-mRNA-Expression in Knochenproben eines Kollektives und in humanen, primären Osteoblastenkulturen in Hinblick auf die differenzierungsabhängige T$\beta$R-Expression und den Einfluß von Dexamethason auf Osteoblasten unterschiedlicher Reife. Verwendet wird eine quantitative 2-Schritt-RT-PCR. $\bf Ergebnisse:$ Signifikante Korrelationen zwischen den T$\beta$R zeigen sich. Die Expression einzelner T$\beta$R ändert sich (signifikant) abhängig von Geschlecht, Hormonstatus, Entnahmeort (T$\beta$R-II), Diagnose (T$\beta$R-II), Gewicht (T$\beta$R-I), Mobilisation und Steroidbehandlung. Steroide wirken auf die T$\beta$R in Abhängigkeit von Inkubationszeit, Dosishöhe und Differenzierungsgrad

Welfare Assessment in Calves Fattened According to the "Outdoor Veal Calf" Concept and in Conventional Veal Fattening Operations in Switzerland.

The "outdoor veal calf" system was developed to encounter the demand for a veal fattening system that allows for reducing antimicrobial use without impairing animal welfare. Management improvements including direct purchase, short transportation, vaccination, three-week quarantine in individual hutches, and open-air housing in small groups in a roofed, straw-bedded paddock with a group hutch were implemented in a prospective intervention study (1905 calves, 19 intervention and 19 control farms, over one year): antimicrobial use was five times lower in "outdoor veal" farms compared to control farms (p < 0.001), but it was crucial to ensure that antimicrobial treatment reduction was not associated with decreased animal welfare, i.e., that sick animals were not left untreated. Welfare was assessed monthly on the farms, and organs of 339 calves were examined after slaughter. Cough and nasal discharge were observed significantly (p ≤ 0.05) less often in intervention than in control farms, mortality (3.1% vs. 6.3%, p = 0.020) and lung lesion prevalence (26% vs. 46%, p < 0.001) were lower; no group difference was seen in abomasal lesion prevalence (65% vs. 72%). Thus, besides reduced antimicrobial use, calf health and welfare were improved in "outdoor veal calf" farms in comparison to traditional operations

To Restore Health, “Do we Have to Go Back to the Future?” The Impact of a 4-Day Paleolithic Lifestyle Change on Human Metabolism – a Pilot Study.

On their way from the Stone Age via the Agricultural Revolution to current high-tech conditions, humans lost their primal foraging behavior. Today, energy expenditure is not necessary anymore for gathering nor hunting, and metabolic diseases are epidemically arising wherever our original Paleolithic lifestyle is turning into a modern sedentary lifestyle. In this pilot study, we followed through the concept that a radical change towards a Paleolithic hunter-gatherer lifestyle could serve as therapy against any metaflammatory disease, even in the short term. Thirteen healthy adult volunteers were transferred to the DELUX National Park (Germany and Luxembourg) for four days and three nights, where Stone Age conditions where mimicked. Thirty-eight biochemical and bioelectrical parameters were measured from participants before and after this relocation. Body weight (-3,9%), body fat (-7,5%), body mass index (-3,8%), visceral fat area (-14,4%) and metaflammation-related parameters (fasting glucose = -18,2%; fasting insulin = -50,1%; HOMA = -57,8%) decreased significantly. C-reactive protein, as the main indicator for low-grade inflammation, increased up to an average of 169,6 %. Our data show that returning to our Paleolithic roots may have positive effects on risk factors commonly associated with metabolic disorders, such as obesity and type 2 diabetes. These findings may lead the way to further research to answer the question whether the already existing metabolic conditions and/or autoimmune and neuroinflammatory diseases could be influenced by a Paleolithic lifestyle

Factors affecting prehospital delay in rural and urban patients with stroke: a prospective survey-based study in Southwest Germany

Background!#!Reducing prehospital delay plays an important role in increasing the thrombolysis rate in patients with stroke. Several studies have identified predictors for presentation ≤4.5 h, but few compared these predictors in urban and rural communities. We aimed to identify predictors of timely presentation to the hospital and identify possible differences between the urban and rural populations.!##!Methods!#!From January to June 2017, we conducted a prospective survey of patients with stroke admitted to an urban comprehensive stroke centre (CSC) and a rural primary care centre (PCC). Predictors were identified using binary logistical regression. Predictors and patient characteristics were then compared between the CSC and PCC.!##!Results!#!Overall, 459 patients were included in our study. We identified hesitation before seeking help, awareness of the existence of a time-window, type of admission and having talked about stroke symptoms with friends/relatives who had previously had a stroke as the strongest predictors for presentation to the emergency room ≤4.5 h. Patients admitted to the rural PCC were more hesitant to seek help and less likely to contact emergency services, even though patients had comparable knowledge pertaining to stroke care concepts.!##!Conclusions!#!Patients from rural areas were more likely to be hesitant to seek help and contacted the EMS less frequently, despite similar self-awareness of having a stroke. Educational campaigns should focus on addressing these disparities in rural populations. Affected patients should also be encouraged to talk about their symptoms and take part in educational campaigns

Regularized reconstruction of digital time-of-flight Ga-68-PSMA-11 PET/CT for the detection of recurrent disease in prostate cancer patients

Accurate localization of recurrent prostate cancer (PCa) is critical, especially if curative therapy is intended. With the aim to optimize target-to-background uptake ratio in Ga-68-PSMA-11 PET, we investigated the image quality and quantitative measures of regularized reconstruction by block-sequential regularized expectation maximization (BSREM). Methods: The study encompassed retrospective reconstruction and analysis of 20 digital time-of-flight (TOF) PET/CT examinations acquired 60 min post injection of 2 MBq/kg of Ga-68-PSMA-11 in PCa patients with biochemical relapse after primary treatment. Reconstruction by ordered-subsets expectation maximization (OSEM; 3 iterations, 16 subsets, 5 mm gaussian postprocessing filter) and BSREM (beta-values of 100-1600) were used, both including TOF and point spread function (PSF) recovery. Background variability (BV) was measured by placing a spherical volume of interest in the right liver lobe and defined as the standard deviation divided by the mean standardized uptake value (SUV). The image quality was evaluated in terms of signal-to-noise ratio (SNR) and signal-to-background ratio (SBR), using SUVmax of the lesions. A visual assessment was performed by four observers. Results: OSEM reconstruction produced images with a BV of 15%, whereas BSREM with a beta-value above 300 resulted in lower BVs than OSEM (36% with beta 100, 8% with beta 1300). Decreasing the acquisition duration from 2 to 1 and 0.5 min per bed position increased BV for both reconstruction methods, although BSREM with beta-values equal to or higher than 800 and 1200, respectively, kept the BV below 15%. In comparison of BSREM with OSEM, the mean SNR improved by 25 to 66% with an increasing beta-value in the range of 200-1300, whereas the mean SBR decreased with an increasing beta-value, ranging from 0 to 125% with a beta-value of 100 and 900, respectively. Decreased acquisition duration resulted in beta-values of 800 to 1000 and 1200 to 1400 for 1 and 0.5 min per bed position, respectively, producing improved image quality measures compared with OSEM at a full acquisition duration of 2 min per bed position. The observer study showed a slight overall preference for BSREM beta 900 although the interobserver variability was high. Conclusion: BSREM image reconstruction with beta-values in the range of 400-900 resulted in lower BV and similar or improved SNR and SBR in comparison with OSEM

Comparison of 68Ga-PSMA-11 PET/CT with 11C-acetate PET/CT in re-staging of prostate cancer relapse

Positron emission tomography (PET) imaging is used to localize recurrent disease in prostate cancer (PCa). The tracer 68Ga-PSMA-11 visualizes lesions overexpressing prostate-specific membrane antigen (PSMA), while 11C-acetate visualizes lesions with increased anabolic metabolism. The aim of this study was to compare the performance of PSMA-PET and acetate-PET in re-staging patients with biochemical relapse. Thirty PCa patients with prostate-specific antigen (PSA) relapse after primary curative therapy were prospectively evaluated. PET/CT examinations using 11C-acetate and 68Ga-PSMA-11 were performed. Identified lesions were categorized according to anatomical location and PET measurements were correlated with PSA at time of scan. Tumour lesions showed higher semi-quantitative uptake values on PSMA-PET than acetate-PET. PSMA-PET identified more lesions in 11 patients, fewer lesions in eight patients, and identical number of lesions in 11 patients. This study indicates better diagnostic performance of PSMA-PET, particularly in detecting lymph node (81% vs 60%, p=0.02) and bone metastasis (95% vs 61%, p=0.0001) compared to acetate-PET. However, 38% of PSMA-expressing metastases appear to be metabolically inactive and 15% of metabolically active metastases lack PSMA expression. Addition of PET with a metabolic tracer, such as 11C-acetate, might be beneficial before making treatment decisions